Bone morphogenetic protein-7 release from endogenous neural precursor cells suppresses the tumourigenicity of stem-like glioblastoma cells

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Item Type:	Article
Title:	Bone morphogenetic protein-7 release from endogenous neural precursor cells suppresses the tumourigenicity of stem-like glioblastoma cells
Creators Name:	Chirasani, S.R., Sternjak, A., Wend, P., Momma, S., Campos, B., Herrmann, I.M., Graf, D., Mitsiadis, T., Herold-Mende, C., Besser, D., Synowitz, M., Kettenmann, H. and Glass, R.
Abstract:	Glioblastoma cells with stem-like properties control brain tumour growth and recurrence. Here, we show that endogenous neural precursor cells perform an anti-tumour response by specifically targeting stem-like brain tumour cells. In vitro, neural precursor cells predominantly express bone morphogenetic protein-7; bone morphogenetic protein-7 is constitutively released from neurospheres and induces canonical bone morphogenetic protein signalling in stem-like glioblastoma cells. Exposure of human and murine stem-like brain tumour cells to neurosphere-derived bone morphogenetic protein-7 induces tumour stem cell differentiation, attenuates stem-like marker expression and reduces self-renewal and the ability for tumour initiation. Neurosphere-derived or recombinant bone morphogenetic protein-7 reduces glioblastoma expansion from stem-like cells by down-regulating the transcription factor Olig2. In vivo, large numbers of bone morphogenetic protein-7-expressing neural precursors encircle brain tumours in young mice, induce canonical bone morphogenetic protein signalling in stem-like glioblastoma cells and can thereby attenuate tumour formation. This anti-tumour response is strongly reduced in older mice. Our results indicate that endogenous neural precursor cells protect the young brain from glioblastoma by releasing bone morphogenetic protein-7, which acts as a paracrine tumour suppressor that represses proliferation, self-renewal and tumour-initiation of stem-like glioblastoma cells.
Keywords:	Cytokines, Glioblastoma, Neoplasia of CNS, Neural Stem Cells, Progenitor Cell, Animals, Mice
Source:	Brain
ISSN:	0006-8950
Publisher:	Oxford University Press
Volume:	133
Number:	Pt 7
Page Range:	1961-1972
Date:	July 2010
Official Publication:	https://doi.org/10.1093/brain/awq128
PubMed:	View item in PubMed

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